Leiomyosarcoma of the urinary bladder in a patient with bilateral retinoblastoma

Authors


Tomonori Minagawa, Department of Urology, Shinshu University 3-1-1, Asahi, Matsumoto, Japan. Email: minagaaa@hsp.md.shinshu-u.ac.jp

Abstract

Abstract:  We report a case of bladder leiomyosarcoma in a 27-year-old woman who had previously been treated with surgery and radiation for bilateral retinoblastoma. The patient was admitted to hospital with discomfort on micturition. Cystoscopy revealed a bladder tumor covered by normal urothelium. Transurethral resection of the bladder tumor was performed, and the histopathological diagnosis was leiomyosarcoma. Partial cystectomy was performed. The leiomyosarcoma of the bladder did not invade the muscle layer. However, bladder tumors recurred at new intravesical locations repeatedly. After transurethral resection of the bladder tumor had been performed twice, total cystectomy and creation of an ileal conduit were performed.

Introduction

Recently, a great deal of attention has been paid to the occurrence of second malignancies following radiation therapy and/or chemotherapy, especially in patients with retinoblastoma.1 In retinoblastoma patients, new primary tumors often arise in the radiation field and chemotherapy for retinoblastoma may also affect the incidence of second malignancies. However, such tumors sometimes occur outside the radiation field or in patients who have not received chemotherapy and the mechanism underlying such tumors is unclear. Second malignancies have been reported to include rhabdomyosarcoma, osteosarcoma, and other malignancies. However, leiomyosarcoma of the urinary bladder in retinoblastoma patients is very rare and only nine cases have been reported. Here, we report a case of recurrent leiomyosarcoma of the bladder in a retinoblastoma patient without any history of chemotherapy.

Case report

A 28-year-old Japanese woman was admitted to hospital with discomfort on urination. At the age of 13 months, she had undergone enucleation of the left eye and radiation therapy to the right eye for bilateral retinoblastoma. She had not received chemotherapy at that time. Her father had a history of renal cell carcinoma, but neither parent had a history of retinoblastoma. Physical examination was unremarkable and there were no abnormal laboratory data, except for the results of urinalysis indicating hematuria and pyuria. The patient underwent cystoscopy, which detected a papillary pedunculated tumor measuring 5 cm in size on the left wall of the bladder (Fig. 1A). The lesion was covered by normal urothelium. Magnetic resonance imaging (MRI) showed a large mass within the bladder lumen and multiple tumors in the uterus (Fig. 1B). No retroperitoneal or pelvic lymphadenopathy or other tumors were seen. The patient underwent transurethral resection of the bladder tumor (TURBT). Histological examination confirmed the diagnosis of bladder leiomyosarcoma covered by normal urothelium (Fig. 2). The tumor was positive for desmin and smooth muscle actin. Partial cystectomy was performed, achieving complete removal of the mass, along with left pelvic lymphadenectomy and intraoperative uterine biopsy. Histological examination confirmed the diagnosis of non-invasive bladder leiomyosarcoma and the resection margins were negative. The uterine tumors were leiomyomas according to histopathological examination and malignant cells were not revealed in the pelvic lymph nodes. Ten months after partial cystectomy, cystoscopy revealed a recurrent bladder tumor covered by normal urothelium, which was distant from the previous surgical margin. Repeat TURBT was performed. Histological examination confirmed the diagnosis of non-invasive bladder leiomyosarcoma like the previous tumor. Six months after the second TURBT procedure, cystoscopy revealed multiple tumors in the bladder resembling the previous lesions. MRI revealed that the uterine masses had also increased in size and number. The uterine tumors were suspected to be malignant. Total cystectomy and creation of an ileal conduit were performed at two years after the first operation. At the same time, resection of the uterine tumors was performed. The leiomyosarcoma did not invade the muscle layer of the bladder histopathologically, while the uterine tumors were leiomyomas without any malignant component. The patient is alive and disease-free at 16 months after the last operation.

Figure 1.

(A) Cystoscopy reveals a papillary pedunculated tumor measuring 5 cm in size on the left wall of the bladder. (B) Magnetic resonance imaging reveals an intravesical tumor and multiple submucosal tumors of the uterus.

Figure 2.

The tumor consists of spindle cells arranged in interlacing bundles and fascicles. The tumor cells have hyperchromatic and moderately pleomorphic nuclei (Hematoxylin–eosin stain, ×400).

A genetic examination was not performed because the patient did not provide consent for the examination.

Discussion

Retinoblastoma is the most frequent ocular malignancy of early childhood. An estimated 40% of retinoblastomas are known to be genetic. The tumor is linked to RB1 gene mutations in all patients with bilateral retinoblastoma, as well as in 10–15% of those with unilateral retinoblastoma. Although the cure rate of retinoblastoma is excellent after extirpation or irradiation, the likelihood of long-term survival in the hereditary group is reduced because of the occurrence of second malignancies a number of years after treatment.

Second malignancies may appear inside or outside the radiation field. These tumors are reported to include rhabdomyosarcoma, osteosarcoma, melanoma, pineoblastoma, and other lesions.1 Reports on the cumulate incidence of second malignancies in retinoblastoma patients are conflicting, ranging from 8.4% at 18 years after diagnosis to 90% after 30 years.1,2 Second malignancies may be associated with the RB1 gene, radiation therapy, and chemotherapy, but the mechanism of tumorigenesis is still mysterious.

Leiomyosarcoma is a mesenchymal malignancy that accounts for 0.2–0.7% of all bladder cancers.3 In retinoblastoma patients, leiomyosarcoma of the urinary bladder is a rare second primary tumor, and only nine cases have been reported in the English published reports (Table 1). In previous articles, the authors have suggested, that cyclophosphamide, which was used for the treatment of previous malignancies (especially retinoblastoma), could have induced leiomyosarcoma of the bladder.4 Although cyclophosphamide may cause DNA damage within the bladder, it is notable that our patient had not received any chemotherapy. Due to its rarity, the association of bladder leiomyosarcoma with Rb gene mutation or chemotherapy is unknown, but p53 mutations are often found together with RB1 abnormalities in soft tissue sarcomas.5 In addition, Bléoo et al. reported a case of leiomyosarcoma of the bladder in a retinoblastoma patient and concluded that loss of RB1 and p53 may contribute to the initiation and/or progression of such leiomyosarcomas based on the results of genetic testing.6 Thus, leiomyosarcoma of the urinary bladder might also be associated with RB1 and p53.

Table 1.  Characteristics of reported cases of leiomyosarcoma of the urinary bladder in patients with bilateral retinoblastoma
Author (Journal)Retinoblastoma therapyBladder leiomyosarcoma
RadiationChemotherapyTreatmentLocation of recurrence
  1. A, adriamycin; CPA, cyclophosphamide; TURBT, transurethral resection of bladder tumor; V, vincristine.

Kawamura J (Urol. Int., 1993)NoCPATotal cystectomyNone
Liang S (Arch. Pathol. Lab. Med., 2001)NoNoTotal cystectomy and chemotherapyLung
Motta L (J. Urol. Nephrol., 2001)NoCPAPartial cystectomyNone
Parekh DJ (Urology, 2002)NoCPA + VTotal cystectomyNone
Bleoo SL (Urol. Int., 2003)YesCPA + V + APartial cystectomyNone
Tanguay C (Mod. Pathol., 2003)NoCPAPartial cystectomyNone
Venkatraman L (J. Clin. Pathol., 2003)YesNoTotal cystectomyNone
Ali A. Al-Zahrani (Saudi Med. J., 2006)YesCPA + VTotal cystectomyNone
Brucker B (Pediatr. Blood Cancer, 2006)NoCPAPartial cystectomy and TURBTBladder
Present caseYesNoPartial cystectomy and total cystectomyBladder

Our patient had leiomyosarcoma of the urinary bladder and was a retinoblastoma survivor without any history of chemotherapy. Her family history of retinoblastoma was negative and genetic examination was not performed because informed consent was not given, but we know that she had bilateral retinoblastoma and a second malignancy of the bladder. Her recurrent bladder tumors were covered with normal urothelium and were far from the location of the previous lesion, which means the recurrent tumors were not intravesical metastasis but were second or third malignancies arising in the bladder. Brucker B et al. reported a similar case of recurrent intravesical leiomyosarcoma with a history of chemotherapy of cyclophosphamide.7 This is the first case of multiple recurrent intravesical leiomyosarcoma as the second malignancy in a retinoblastoma patient without any history of chemotherapy. It suggests that not only the RB1 gene and chemotherapy, but also other genetic factors, might be associated with bladder leiomyosarcoma in retinoblastoma patients. Genetic examination was not performed in this case, so the mechanism underlying the occurrence of leiomyosarcoma and leiomyoma was not defined.

Although partial cystectomy has been the most common treatment in the previous reports, total cystectomy may be more suitable for the treatment of bladder leiomyosarcoma in retinoblastoma survivors because of the possibility of intravesical recurrence like that in this case.

Our patient also had multiple large leiomyomas in the uterus. Simultaneously occurring benign uterine leiomyomas have been described.8,9 An association of retinoblastoma with leiomyoma has not been reported.

Ancillary